New types of medicines need new regulatory approaches

Original Article

As physicians, we are excited by new medical advances undreamed of only a few decades ago.

Scientists are now creating advanced and truly individualized medicines that work with a person’s unique set of bodily components, such as DNA. Many of these new medicines – “biologic” drugs – are much more complicated than previous generations of medicines.

Biologics are large, complex molecules, produced by genetic engineering techniques and manufactured by living cells. The everyday drugs that we are all familiar with, such as aspirin, are small in molecular weight and made by chemical reactions. Mixing the same chemicals in the same way always gives the same predictable outcome.

In comparison, biologics are not the result of a chemical reaction but are “grown” in cells biologically engineered for this purpose.

As a result, biologic drugs grown using different cell lines or different manufacturing processes are not identical. They are variants of the original drug, each containing different contaminants produced by the living cells used in the production process.

These unavoidable contaminants can cause different allergic (immune) responses. On average, biologic drugs cost more than $1 billion and often take more than 10 years to be created and tested before they are available for patient use.

Now that some patents on some older biologic drugs are expiring, generic pharmaceutical companies are looking to enter the market with variant products, similar to the original, innovative drug. These new drug versions would open the market to competition and cost savings.

But because the replicated variant drugs – called “follow-on biologic” or “biosimilar” drugs – aren’t identical to the original drug, they are not true generic or “bioidentical” drugs.

In reality, these drugs should be called “biodifferent” because it is the differences and not the similarities that concern us.

In response to this new class of drugs, Congress is considering ways to appropriately create new Food and Drug Administration approval pathways for follow-on biologics.

Rep. Henry Waxman, D-Calif., has introduced HR 1427; Washington Congressman Jay Inslee, D-Bainbridge Island, is one of the sponsors of HR 1548.

Both bills recognize the difference between older and simpler generic drugs and the newer, much more complicated biologics. But they take significantly different approaches to testing drug risks and to providing incentives for future innovation and intellectual property protection.

The Waxman approach essentially acknowledges that a follow-on biologic is not identical to the innovator drug. But it considers a follow-on drug to be “close enough” to the innovator drug and, therefore, would allow for an abbreviated, less thorough drug-approval process than used with the original medicine. The intent would be to save money and speed introduction of the new drug.

In contrast, HR 1548’s approach would require more clinical testing and monitoring of the risks and efficacy of the follow-on biologics, a process that has been successfully adopted by the European Union.

The approval process is important because seemingly small differences in drugs can cause very significant adverse events in the body. Because biologics are hugely complex entities, predicting the risks and effectiveness of follow-on biologics is impossible.

For example, a biologic form of erythropoietin (a hormone stimulating production of red blood cells) is available in the United States and Europe. Despite the complete cooperation of the two companies producing the medicine, the products aren’t identical. Slight differences caused different and sometimes devastating immune responses in the European version.

Every moment of a physician’s working day is devoted to helping patients live healthier lives and to treating their ailments more safely and effectively. What is “close enough” for government work in Waxman’s bill might not be close enough for our patients. Because of the greater diversity of possible treatments, biologics require more highly individualized care. The physician and the patient are partners in the appropriate use of these new medicines.

Government agencies can’t predict the future any better than anybody else and, by definition, can’t predict innovation. The FDA is therefore often behind the times in dealing with any new class of drugs.

We believe the Inslee bill would better enhance development of these innovative drugs; Congress should act quickly to enact it. It’s the better approach to helping patients access these promising medical treatments.

Robert J. Cihak, M.D., of Brier in Snohomish County, is a senior fellow in medicine at the Discovery Institute. Richard Dolinar, M.D., is a private practice clinical endocrinologist in Phoenix, Ariz., and a senior fellow in health care policy at The Heartland Institute.

Dr. Robert J. Cihak, M.D.

Robert J. Cihak, M.D., was born in Yankton, South Dakota. He received his Bachelor's Degree from the University of Notre Dame, Indiana, where he studied under the philosopher Eric Voegelin. He earned an M.D. degree at Harvard Medical School (1962-66), and did postgraduate medical training and academic work as a surgical intern at Stanford Medical Center (1966-67), diagnostic radiology resident at the Massachusetts General Hospital (MGH) in Boston (1967-70) and Assistant Professor of Radiology, U. New Mexico Medical School, Albuquerque, (1970-71). He then practiced diagnostic radiology in Aberdeen Washington until his retirement in 1994.